Mirofluidic device wherein the liquid/fluid interface is stabilized

ABSTRACT

The microfluidic device comprises at least one microchannel bounded by a bottom wall, side walls and a top wall and which is designed to contain at least one liquid and at least one fluid non-miscible with the liquid. The microfluidic device comprises means for stabilizing the interface between the liquid and the fluid. The means for stabilizing comprise at least one electrode arranged on at least one part of a first wall of the microchannel, over the entire length thereof, and at least one counter-electrode arranged over the entire length of the microchannel, on at least one part of a second wall, arranged facing the electrode. The electrode and counter-electrode are preferably respectively arranged on the bottom and top wall of the microchannel.

BACKGROUND OF THE INVENTION

The invention concerns a microfluidic device comprising at least onemicrochannel designed to contain at least one liquid and at least onefluid non-miscible with the liquid and means for stabilizing theinterface between the liquid and the fluid, said microchannel beingbounded by a bottom wall, side walls and a top wall.

STATE OF THE ART

Microlabs or microfluidic devices, better known as μ-TAS (micro TotalAnalysis System) or Lab-on-a-chip, are used to perform chemical orbiological operations on samples of very small volumes. These volumesare for example of an order of magnitude comprised between a nanoliterand a microliter. It is thus known to use microfluidic devices toperform mixtures, separations, temperature checks, reactions orextractions by solvent.

On this scale, one of the major difficulties arising from placing twophases non-miscible with one another in contact and, more particularly,when mass transfer takes place between the two phases, in the case of anextraction by solvent for example, is stabilization of the interfacebetween the two phases.

Different method exist for stabilizing liquid/liquid or liquid/gasinterfaces. Thus, in larger scale devices, it is known to stabilize theinterface between two non-miscible phases by means of a porous membrane.For example, the document WO-A-9,612,540 describes a device and aprocess enabling transfer of solutes between two non-miscible fluidphases, through a flat porous membrane designed to stabilize theinterface between the two fluid phases.

This technique has been adapted to the scale of microlabs, as mentionedby the document “Fabrication of components and systems for chemical andbiological microreactors” by W. Ehrfeld et al. (Microreactiontechnology, IMRET1, 1997, pages 72-90). This document describes the useof very fine, selective membranes in microlabs to perform extractionsand filtrations.

It is also known to modify the surface properties of a microchannelwherein two phases non-miscible with one another are placed. Thus, thedocument “Surface-directed liquid flow inside microchannels” by Bin Zhaoet al. (Science, Vol 291, 2001, pages 1023-1026), describes a method forinterface stabilization in a microchannel. Predetermined zones of thebottom of the microchannel are chemically treated so as to modify thewettability properties of the zones, which imposes particular paths onthe two phases. Each phase in fact remains localized on the zone thatcorresponds the best thereto from a wettability standpoint. Thistechnique is in particular used for applications where a large contactsurface between the two phases is necessary but it is not very practicalto implement.

It is also commonplace to apply a potential difference non-continuouslybetween two electrodes for the purpose of moving a fluid from one givenpoint to another. Thus, the document US-A-2002/043,463 describes adevice designed to make a drop of electrolyte arranged in a non-miscibleliquid move from a lower chamber to an upper chamber via orificesarranged in a wall separating the upper chamber from the lower chamber.Non-continuously applying a potential difference between a first coupleof electrodes enables the drop to be moved, in a first step, along thelower chamber to bring it to face a predetermined orifice of the wall.Then a potential difference is applied non-continuously between a secondcouple of electrodes arranged respectively under the lower chamber andon the upper chamber so as to enable the drop to go from one chamber tothe other through the orifice of the wall.

The documents U.S. Pat. No. 4,818,052 and WO-A-02,069,016 describeoptical switches operating by means of the movement in a microchannel ofa first fluid with respect to a second fluid non-miscible with the firstfluid, between first and second positions. Movement of the first fluidcan be achieved by non-continuously applying a potential differencebetween electrodes arranged on the opposite walls of the microchannel.Each electrode covers a part of the length of the microchannel so as tocause a longitudinal movement of the drop inside the microchannel byapplying a sequence of control signals.

Application of a voltage in this type of device only enables a fluid tobe moved in another non-miscible fluid and from one given point toanother given point.

OBJECT OF THE INVENTION

The object of the invention is to provide a microfluidic device whereinthe contact zone between a liquid and a fluid, non-miscible with oneanother, is stabilized and is easy to implement, while preserving a highcontact surface between the liquid and the fluid.

According to the invention, this object is achieved by the fact that themeans for stabilizing comprise at least one electrode arranged on atleast one part of a first wall of the microchannel, over the entirelength thereof, and at least one counter-electrode arranged over theentire length of the microchannel, on at least one part of a second wallarranged facing the electrode.

According to one development of the invention, the counter-electrode isarranged on the whole of the second wall.

According to a preferred embodiment, the electrode and counter-electrodeare respectively arranged on the bottom and top wall.

According to another feature of the invention, the fluid or liquid beingelectrically conducting, the microfluidic device comprises insulatingmeans arranged between the electrode or counter-electrode and said fluidor said liquid.

According to another feature, the microchannel comprises, at least atone end, two end microchannels designed for the fluid and the liquid torespectively flow therethrough.

BRIEF DESCRIPTION OF THE DRAWINGS

Other advantages and features will become more clearly apparent from thefollowing description of particular embodiments of the invention, givenas non-restrictive examples only and represented in the accompanyingdrawings, in which:

FIG. 1 is a schematic representation, in cross-section, of amicrofluidic device according to the invention.

FIGS. 2 and 3 respectively represent different embodiments of amicrochannel of a microfluidic device according to the invention.

FIGS. 4 to 7 schematically represent, in top view, different steps ofintroducing a liquid and a fluid into a microfluidic device according tothe invention.

FIGS. 8 to 11 are schematic representations of different steps ofachievement of a microfluidic device according to the invention.

DESCRIPTION OF PARTICULAR EMBODIMENTS

In FIG. 1, a microfluidic device 1, in particular used to performextractions by solvent, comprises at least one microchannel bounded by abottom wall 2 formed by a substrate 3, side walls 4 formed on thesubstrate and a top wall 5 parallel to the substrate. The microchannelis designed to bring a liquid and a fluid forming two phases 6 and 7non-miscible with one another into contact. What is meant by a fluid isa liquid or a gas.

The microchannel is a hollow three-dimensional structure presenting avery great length with respect to the height. In the case where thelength is very great with respect to the width, a microchannel of linearthree-dimensional structure will be referred to. For example, the lengthof a microchannel is preferably about a few millimeters to a fewcentimeters, whereas the width and height are respectively about a fewtens to a few hundreds of micrometers. The microchannel can also have avery great width with respect to its height, in particular when itcontains a large number of phases. A microchannel of surfacethree-dimensional structure or a microchamber will then be referred to.

To stabilize the interface between two phases, the microfluidic devicecomprises at least one electrode arranged on at least one part of afirst wall of the microchannel, over the entire length of the latter. Atleast one counter-electrode is arranged over the entire length of themicrochannel, on at least one part of a second wall. The part of thesecond wall that comprises the counter-electrode is arranged facing theelectrode. The counter-electrode can also be arranged on the whole ofthe second wall. The width of the electrode and of the counter-electrodeis preferably about a few tens to a few hundreds of micrometers.

The microfluidic device also comprises means designed to create apotential difference between the electrode and counter-electrode. Thepotential difference creates forces called electrostatic forces whichmodify certain properties of one of the two phases or of both thephases, depending on the sensitivity of the phases with respect to theseforces. Thus, the forces can be of different natures, depending on thecharacteristics of the liquid and fluid placed in contact. They can forexample modify the wetting characteristics of one of the phases or ofboth phases with respect to their support. In this case, the forces arecalled electrowetting or electrocapillarity forces. Volumetric forces ordielectric forces acting on dielectric liquids can also be involved.

The potential difference created enables the phase that is the mostsensitive to the forces created to be kept in a zone bounded by theelectrode and the part of the counter-electrode arranged facing theelectrode, which stabilizes the interface between the two phases, whichinterface can be vertical or horizontal according to the arrangement ofthe electrodes. Thus, if the electrode and counter-electrode arerespectively arranged on the bottom wall and the top wall, the interfaceis substantially vertical, whereas if the electrodes are arranged on theside walls, the interface is substantially horizontal.

In FIG. 1, the electrode 9 is arranged on a part of the bottom wall 2and the counter-electrode 10 is arranged on the whole of the top wall 5.The electrode 9 and counter-electrode 10 are respectively in contactwith the phase 7 and the two phases 6 and 7. The electrode 9 and thepart of the counter-electrode 10 facing the electrode 9 then form afirst predetermined zone in which the phase 7 is located, the phase 8being arranged in a second zone of the microchannel located next to thefirst zone.

The device also comprises an electrical contact connection 11 whichconnects the electrode 9 to a voltage generator 12, also connected tothe counter-electrode 10. The voltage applied by the generator is eitherAC or DC and it is about a few tens to a few hundreds of Volts. In thecase of an AC voltage, the electrical frequency can range from about afew tens of Hertz to a few tens of megaHertz. Thus, the voltage createdbetween the two electrodes is permanent, i.e. it is not applied fromtime to time but on the contrary throughout the use of the microfluidicdevice, so that during this time, the interface between the two phasesis stabilized. The voltage can for example be sinusoidal.

The phases inlet to the microchannel can be immobile or in movement. Ifthe phases are intended to be in movement, the microchannel cancomprise, at least at one end, two end microchannels designed for thefluid and liquid to respectively flow therethrough. Thus, in FIG. 2, theliquid and fluid are designed to flow in a microchannel 13, respectivelyin first and second longitudinal and adjacent zones. The first zone isbounded, in FIG. 2, by the electrode 9, whereas the second zonecorresponds to the free part of the microchannel, i.e. the part notcomprising an electrode. The microchannel 13 also comprises bends so asto occupy less space than a linear microchannel.

The ends of the microchannel 13 respectively comprise an inletmicrochannel 14 and an outlet microchannel 16, respectively designed forinlet and outlet of a first phase. Likewise, for inlet and outlet of asecond phase, the two ends of the microchannel 13 comprise an inletmicrochannel 15 and an outlet microchannel 17. The two phases flow inthe microchannel 13 on paths bounded by the electrode andcounter-electrode. The path of the phase that is the most sensitive tothe potential difference created between the electrode andcounter-electrode is represented by the electrode 9 in FIG. 2. Thelatter is arranged on a part of the width of the bottom wall of themicrochannel 13, over the entire length of the latter, and over theentire length and width of the inlet and outlet microchannels 15 and 17.The two phases can flow in the same direction or in opposite directions.

According to alternative embodiments, the microfluidic device cancomprise a plurality of microchannels arranged in series or in parallel.Thus, in FIG. 3, the microchannel 13 according to FIG. 2 is connected toa second microchannel 18 of the same geometry. The second microchannel18 comprises an inlet microchannel 19 for introducing a third phase andan inlet microchannel 20 for introducing the first phase. The inletmicrochannel 20 is connected to the outlet microchannel 16 so as toenable the first phase to flow from the first microchannel 13 to thesecond microchannel 18. This enables a second mass transfer to beperformed between the first and third phases, the second phase of thefirst microchannel 13 being removed via the outlet microchannel 17.Placing several microchannels in series thus enables several successiveextractions to be performed, whereas placing several microchannels inparallel enables several extractions to be performed simultaneously.

The two phases can be injected into the microfluidic device by anysuitable means. Thus, the liquid and fluid can be injected by means of apump, a water column or a plunger syringe or by capillarity orelectro-osmosis. Thus, as represented in FIGS. 4 to 7, the microchannel13 comprises a tank 21 designed to receive the second phase 7. Acapillary 22 is also connected, by sticking, to one of the inlets of themicrochannel 13, so as to inject the first phase.

In FIG. 5, a volume of the second phase 7 is deposited in the tank 21.Due to the action of the potential difference applied between thecounter-electrode (not shown) and the electrode 9, the second phase 7,which is the most sensitive to the potential difference, spreads in thezone bounded by the electrode 9 and the part of the counter-electrodefacing the electrode 9 (FIG. 6). The forces created by the potentialdifference also play the role of a microfluidic pump, driving the secondphase 7 into the zone of the microchannel 13 represented by theelectrode 9 in FIG. 5. Once the second phase 7 has been injected andstabilized, the first phase 6 is injected via the capillary 22 (FIG. 7)and flows in the microchannel 13, in the free space of the microchannel13. The interface 8 between the first and second phases 6 and 7 remainsstable during this flow.

The microfluidic device according to the invention thus enables theinterface between two phases non-miscible with one another to bestabilized efficiently, without requiring a physical barrier between thetwo phases. This presents the advantage of not reducing the contactsurface between the two phases and therefore of not limiting the masstransfer between the two phases to a small surface.

According to a first embodiment represented in FIGS. 8 to 11, themicrofluidic device according to FIG. 1 is achieved from a substrate 3made of glass or silicon with a thickness of 500 μm, whereon a goldelectrode 9 is achieved by photolithography (FIG. 8). If the liquid orthe fluid are electrically conducting, the microfluidic device comprisesinsulating means enabling the electrode and/or the counter-electrode tobe protected from the conducting liquid and/or fluid. The insulatingmeans are arranged between the electrode or the counter-electrode andthe liquid or fluid. The substrate 3 comprising the electrode can thusbe electrically insulated, for example, by means of a layer 23 ofsilicon oxide or SiO₂ (FIG. 9), said layer being deposited on thesubstrate by means of a plasma enhanced chemical vapor deposition(PECVD) process.

Side walls 4, made of thick resin, are then made on the substrate 3 byphotolithography (FIG. 10). The top wall 5, made of glass or plasticmaterial such as polycarbonate for example, is assembled by screenprinting of glue 24 on the assembly (FIG. 11). Before this step, a partof the width of the top wall 5 has been coated with a layer of an IndiumTin Oxide (ITO) compound. Said layer forms the counter-electrode 10 andmay be electrically insulated. Achieving such a microfluidic devicepresents the advantage of being easy to implement.

The insulating layer 23 of a few micrometers can be made of aninsulating polymer, such as a dimer of the Di Para Xylylene type morecommonly known under the brand name of Parylene®, deposited in vaporphase after the side walls have been achieved. The layer can also bemade of liquid fluorinated polymer, such as liquid Teflon®, deposited byspin coating before assembly by screen printing of glue. Insulation ofthe counter-electrode 10 is for example performed on the top wall beforeassembly. It can be achieved by means of deposition of an insulatinglayer of a few micrometers of Parylene® or Teflon®, deposited accordingto the techniques already described for insulation of the electrode 9.Insulation of the electrode and counter-electrode can also be performedafter assembly of the bottom and top walls by depositing an insulatinglayer of a few micrometers of Parylene® (vapor phase deposition) orliquid Teflon® (deposition by flowing in the microchannel).

According to a second embodiment, the microchannel is achieved in thetop wall 5 by hot embossing. The top wall thus structured is then coatedwith a layer of ITO to achieve the counter-electrode. Assembly of thetop wall on the substrate comprising the electrode is then performed byscreen printing of glue. If the fluid and/or liquid are electricallyconducting, insulation of the electrode and of the counter-electrode isperformed by one of the techniques described in the first embodiment.

The invention is not limited to the embodiments described above. Thus,the electrode and counter-electrode can be respectively arranged on theside walls of the microchannel.

The electrode and counter-electrode can also be arranged facing oneanother, on the whole of a first and a second wall. As the fluid and theliquid do not react in the same way to the potential difference appliedbetween the electrode and the counter-electrode, the interface betweenthe fluid and the liquid is then stabilized by application of thepotential difference.

Moreover, the microfluidic device can contain a number of phases greaterthan two, each phase being non-miscible with the neighboring phases. Itis also possible to couple this technique with already known techniquessuch as the use of a porous membrane or chemical treatment of the wallsof the microchannel.

1-7. (canceled)
 8. Microfluidic device comprising at least onemicrochannel designed to contain at least one liquid and at least onefluid non-miscible with the liquid and means for stabilizing theinterface between the liquid and the fluid, said microchannel beingbounded by a bottom wall, side walls and a top wall, microfluidic devicewherein the means for stabilizing comprise at least one electrodearranged on at least one part of a first wall of the microchannel, overthe entire length thereof, and at least one counter-electrode arrangedover the entire length of the microchannel, on at least one part of asecond wall arranged facing the electrode.
 9. Microfluidic deviceaccording to claim 8, wherein the counter-electrode is arranged on thewhole of the second wall.
 10. Microfluidic device according to claim 8,wherein the electrode and counter-electrode are respectively arranged onthe bottom and top wall.
 11. Microfluidic device according to claim 8,wherein the electrode and counter-electrode are respectively arranged onthe side walls.
 12. Microfluidic device according to claim 8, whereinthe fluid or liquid being electrically conducting, the microfluidicdevice comprises insulating means arranged between the electrode orcounter-electrode and said fluid or said liquid.
 13. Microfluidic deviceaccording to claim 8, wherein the fluid flows in the microchannel in anopposite direction to that of the liquid
 14. Microfluidic deviceaccording to claim 8, wherein the microchannel comprises, at least atone end, two end microchannels designed for the fluid and the liquid torespectively flow therethrough.